Role of HSP27/HSPB1 on the response to treatments in breast cancer

CAYADO-GUTIERREZ N; CIOCCA DR; CASTRO G

Montevideo

Conferencia; Second Latin America Chapter Conference of Cell Stress Society International; 2016

Cell Stress Society International

HSP27 is an ATP-independent molecular chaperone and provides thermo-tolerance in vivo, cytoprotection and cell survival under stress conditions. While some authors have demonstrated upregulation and induced phosphorylation of HSP27 associated to breast tumor growth, drug resistance and a bad prognosis, others have described contradictory results. Therefore, the exact role of this protein in multidrug resistance (MDR) is still under investigation. Recently, HSP27 overexpression has been described as a novel mechanism to sensitize MDR cancer MCF-7/ADR (ADR: Adriamycin) cells to chemotherapy. The authors hypothesize that HSP27 down regulation leads to the accumulation of mutant p53 (HSP27 is known to increase proteasomal p53 degradation) which can lead to the induction of p-glycoprotein efflux pumps. Moreover, alternative therapeutic strategies are being studied in breast cancer, for example administering resveratrol a natural agent that can be an effective adjuvant. It inhibits HSP27 expression and sensitizes tumor cells to doxorubicin treatment. HSP27 also plays a role in the maintenance and chemoresistant character of breast cancer stem cells (BCSCs). HSP27 inhibition increases the suppressive effect of HSP90 inhibitors such as geldanamycin in BCSCs. In addition, HSP27 seems to be involved in the cellular response to actinomycin D (Act D); the HSP27 knockdown enhances Act D-induced caspase activation and apoptosis in breast cancer cells. In summary, multiple signaling pathways can be involved in drug resistance mechanisms. The significance of HSP27 as a marker of resistance is controversial and its interpretation in cancer therapy should be further investigated.